It is known that glycosylurea derivatives manifest biologically active properties and are useful in medicine as active components for the preparation of pharmaceutical compositions. It is also known that glycosylurea derivatives subjected to nitrosation result in substances possessing antitumor properties.
Methods for the synthesis of glycosylnitrosourea with different positions of N-nitrosourea fragments in the carbohydrate ring and with different substituents have been developed in the attempts to obtain selective-effect preparations possessing a good water-solubility and a low toxicity.
The synthesis of these derivatives is based on a general procedure involving interaction of glycosylamine with alkylisocyanates and nitrosation of the reaction products with such nitrosation agents as NaNO.sub.2, NOCl, N.sub.2 O.sub.3, C.sub.5 H.sub.11 NO (cf. U.S. Pat. No. 4,157,439; U.S. Pat. No. 4,156,777; British Patent Application No. 1,539,500; No. 1,507,099; J. Med. Chem., 1979, 22, No. 3, 314-316; J. Med. Chem., 1975, 18, 104).
Numerous glycosylnitrosourea derivatives have been prepared by the reaction of a monosaccharide with an alkylamine, followed by treatment of the resulting glycosylamines with an alkylisocyanate. The reaction results in the preparation of substituted anomeric glycosylurea derivatives which, under the effect of formic acid, are isomerized into a thermodynamically stable form of glycosylurea. The thus-obtained glycosylurea is subjected to nitrosation to give glycosylnitrosourea derivatives (J. Med. Chem., 1982, 25, No. 4, 441-446; Chem. Pharm., Bull 1982, 30, 534-543).
Known in the art is a method for the synthesis of N-chloroethyl-N'-(.beta.-D-glycosyl)-N-nitrosourea comprising reacting poly-O-acetyl-glycosylamines with chloroethylisocyanate in an inert medium, followed by desacetylation of the resulting poly-O-acetyl-glycosylchloroethylurea. Then the desacetylation product is subjected to nitrosation (cf. Bull. Chem. Soc., Japan 48 (12), 3763 (1975)).
Also known is a method for preparing N-alkyl-N'-(.beta.-D-glycosyl)-N-nitrosourea from polyacetylglycopyranose. Polyacetylglycopyranose is synthesized according to a known procedure (P. A. Levene et al., J. Biol. Chem., 90, 89 (1931). Polyacetylglycopyranose is treated with HBr, the resulting poly-O-acetylglycosylbromide is reacted with NaNO.sub.3 and the thus-obtained poly-O-acetylglycosylazide is hydrogenated in the presence of Raney nickel or platinum, or palladium under the pressure of 3.4 kg/cm.sup.2. As a result, poly-O-acetyl-glycosylamine is obtained which is reacted with an alkylisocyanate, followed by isolation of poly-O-acetyl-(.beta.-D-glycosyl)alkylurea. The poly-O-acetyl-(.beta.-D-glycosyl)-alkylurea is desacetylated and then subjected to nitrosation, followed by isolation of the desired product (cf. U.S. Pat. No. 4,086,415). However, this method consists in many steps and is difficult to perform on a commercial scale.